Centre for Inflammatory Diseases, Monash University School of Clinical Sciences, Monash Medical Centre , Melbourne , Australia.
Lupus Sci Med. 2015 Aug 20;2(1):e000105. doi: 10.1136/lupus-2015-000105. eCollection 2015.
Guidelines for azathioprine (AZA) use in systemic lupus erythematosus (SLE), including indications for initiation and cessation, are lacking. Clinical decision-making could be improved if reasons for cessation of AZA treatment were standardised.
We determined the characteristics of AZA use in a cohort of patients with SLE and evaluated reasons for AZA cessation. Patients with SLE in a single centre had longitudinal recording of disease activity (Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI)-2k), laboratory investigations and treatment from 2007 to 2012.
Of 183 patients studied, 67 used AZA on at least one occasion. There was no significant difference between AZA users and non-users in age or American College of Rheumatology criteria. Compared with those not treated with AZA, patients treated with AZA had higher disease activity (time-adjusted mean SLEDAI 5.2±0.3 vs 3.8±0.3, p=0.0028) and damage (Systemic Lupus International Collaborating Clinics (SLICC)-SDI 1.6±0.3 vs 1.2±0.1, p=0.0445), and were more likely to have a positive dsDNA (p=0.0130) and receive glucocorticoids (p<0.0001). AZA therapy was ceased in 30/67 (45%) patients. The predominant reasons for cessation were treatment de-escalation 14 (47%), treatment failure 12 (40%) and toxicity 3 (10%). AZA was switched to mycophenolate mofetil (MMF) in 9/12 (75%) of treatment failures, and this choice was strongly associated with active lupus nephritis.
AZA toxicity was uncommon, and many patients ceased therapy in the context of treatment de-escalation. However, the frequent development of active lupus nephritis requiring MMF suggests the need to distinguish refractoriness, under-treatment and non-adherence to AZA in patients with SLE. These findings suggest that future studies of AZA metabolite measurement could prove valuable in the management of SLE.
目前缺乏关于硫唑嘌呤（AZA）在系统性红斑狼疮（SLE）中的使用指南，包括起始和停药的适应证。如果能使 AZA 停药的原因标准化，临床决策就能得到改善。
我们对单个中心的 SLE 患者队列中 AZA 的使用情况进行了特征描述，并评估了 AZA 停药的原因。2007 年至 2012 年，该中心对每位患者进行了疾病活动度（系统性红斑狼疮疾病活动指数 2000 版（SLEDAI-2k））、实验室检查和治疗的纵向记录。
在 183 例研究患者中，67 例至少有一次使用过 AZA。AZA 使用者与非使用者在年龄或美国风湿病学会标准方面无显著差异。与未接受 AZA 治疗的患者相比，接受 AZA 治疗的患者疾病活动度更高（经时间校正的平均 SLEDAI 为 5.2±0.3 比 3.8±0.3，p=0.0028），且损伤更严重（系统性红斑狼疮国际合作临床中心（SLICC）-SDI 为 1.6±0.3 比 1.2±0.1，p=0.0445），且 dsDNA 阳性的可能性更大（p=0.0130），接受糖皮质激素的可能性更高（p<0.0001）。AZA 治疗在 30/67（45%）患者中停止。停药的主要原因是治疗降级 14（47%）、治疗失败 12（40%）和毒性 3（10%）。AZA 治疗失败的 12 例患者中有 9 例（75%）换用霉酚酸酯（MMF），这种选择与狼疮性肾炎活动密切相关。
AZA 毒性并不常见，许多患者在治疗降级的情况下停止了治疗。然而，频繁发生需要 MMF 治疗的活动性狼疮肾炎提示，需要在 SLE 患者中区分 AZA 的耐药性、治疗不足和不依从性。这些发现表明，未来对 AZA 代谢物测量的研究可能对 SLE 的治疗有价值。
